Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people

Randomized, four-way crossover trial in healthy men and women aged 55-64 years without sleep complaints. Sixteen participants were enrolled; per-protocol analyses included 15 participants for each active arm.

Prolonged-release melatonin 2 mg was given as a single oral dose at 21:00 in a four-way crossover study, with temazepam 20 mg, zolpidem 10 mg, and placebo as comparators. The melatonin product was a tablet formulation; treatment was assessed over nocturnal sleep EEG after one night of dosing.

Prolonged-release melatonin produced only minor EEG effects and did not significantly change slow-wave activity over the entire night versus placebo. Slow-wave activity decreased after prolonged-release melatonin versus placebo only during the first third of the night (p=0.0093). In contrast, temazepam and zolpidem suppressed slow-wave activity compared with placebo, and temazepam reduced activity more than zolpidem across all three slow-wave ranges. The authors concluded that the EEG effects of prolonged-release melatonin are small and likely differ mechanistically from benzodiazepine and non-benzodiazepine hypnotics.

Very small sample size and per-protocol analyses of only 15 participants per active arm limit precision. The trial was conducted in healthy middle-aged adults without sleep complaints, so generalizability to people with insomnia or other sleep disorders is limited. Outcomes were short-term, nocturnal EEG measures from a crossover design, so clinical sleep benefit cannot be inferred directly.